The specific aim of this Australasian center-specific proposal is to renew activities as part of a six-center consortium known as the Cooperative Family Registry (CFR) for colorectal cancer. The aim of the CFR is to accrue colorectal cancer families according to a protocol that includes the generation of a repository of biospecimens (blood and tumour samples), and comprehensive lifestyle data obtained through standardized epidemiologic questionnaires, so as to support research from groups within and outside the CFR To achieve this, over the next five years we will: 1. Recruit 320 population-based colorectal cancer cases diagnosed before the age of 50, regardless of family history, and 250 clinic-based families with at least three cases, as part of the Accrual Component. 2. Not 'contribute to the Minorities Component. 3. Conduct follow-up activities with all subjects (except controls and relatives of controls) who consented to be participants in the CFR during the first phase of recruitment and data collection (July 1997 - July 2002), as well as all new participants who will be recruited in Year 01 to 04 of the renewal in 1. above. We plan both active follow-up at 4 and 6 years after original enrolment, and annual passive follow-up, including a Newsletter. We estimate that our follow-up will involve 10,217 individuals in 1,356 families. 4. Participate in the Molecular Characterization Component by contributing appropriate samples to GMP and the participating CFR laboratories. We estimate that we will prepare, ship, and track samples as follows: 556 for DNA sequencing, 856 for methylation, and 126 samples for GMP conversion mutation analysis. 5. Maintain the biospecimens repository comprising blood samples and tumor blocks and/or paraffin sections and respond to approved requests for samples. 6. Maintain our bioinformatics support activities so that we can respond to queries from CFR and non-CFR investigators, support local analyses, and coordinate activities with the Informatics Support Center (ISC). 7. Develop and maintain a fresh frozen tissue repository on selected, newly diagnosed cases that will contain tissues from 30 colorectal cancers or polyps obtained per year from subjects treated within Queensland. 8. Conduct Pilot studies that will continue the innovative molecular and pathology work by Professor Jess and his laboratory to further unravel the genetic heterogeneity of hereditary colorectal cancer. We shall use the results of the statistical Pilot Study to develop the machinery for analyzing the accrued data, make blood collection and extension of families more efficient and informative, and provide a better resource for future gene discovery. I